tbuckley/cabot-search huggingface dataset:
P1351: REAFFIRMING HEMATOPOIETIC PROGENITORS LINEAGE COMMITMENT BY TRANSCRIPTIONAL ATLAS
Authors: Yongjian Yue, Guoqiang LI, Xuezhao Lin, Sujin Chen
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Deciphering the hematopoiesis mechanism that underlies progenitor cells definition and fate decision are critical to understanding fundamental questions of hematopoietic lineage c ommitment. Classic and traditional surface markers are often speciosity, inefficient and inaccurate for defining hematopoietic progenitor cells. Aims: The transcriptional atlas and the lineage commitment of hematopoietic progenitors (HPCs) in adult peripheral blood remains to be elucidated. Methods: Herein, we reaffirmed the adult hematopoietic progenitors, and recovered the key transcript factors in lineages fate decision, and restructured the lineage commitment model of HPCs by single-cell sequencing. Results: We demonstrated the transcription atlas data of original status HPCs in adult peripheral blood with large number of HPCs. An elaborate and comprehensive transcriptional atlas of all types of hematopoietic progenitors was then constructed. The reaffirmed lineage commitment also revealed hematopoiesis was a continuum procedure controlled by the activation and suppression of transcription factors, with relative identified boundary. Several key factors, including NFE2, LYL1, MYB, and RUNX1 of myeloid and RUNX2, HOXA9, and BCL11A of lymphoid progenitors, were identified as major switches that controlled hematopoietic lineage formation. Our study further reaffirmed and established a comprehensive model of hematopoiesis that can reconcile previous models and explain the conflict among functional studies. Summary/Conclusion: Taken together, our transcriptional atlas of HPCs established a comprehensive continuum and key regulators controlled model of the human adult peripheral blood hematopoiesis. Toward this transcriptional atlas, it provides accurate definition, hierarchy, and biological insights of hematopoiesis and lineage commitment of HPCs. Importantly, this can enable new research development in cell engineering, regenerative medicine, and disease treatment. We are the first to clearly depict the transcriptional atlas and defined each subgroups of adult peripheral blood progenitor. Our results will enable the whole map of the transcriptional signal and pathway among lineage commitment. Moreover, we are also the first to identify the cell fate decision transcriptional factors in each branches among hematopoietic hierarchy formation. The precise control on the hematopoietic progenitor cells priming and differentiation can then be interfere by the key transcriptional factors and receptors signals, which we called Artificial Operation of HPCs.Keywords: Stem cell marker, Differentiation, Peripheral blood progenitor cell, Hematopoietic stem and progenitor cells
P1630: A 2022 CROSS-NATIONAL SURVEY OF PEOPLE LIVING WITH HAEMOPHILIA DURING THE COVID-19 PANDEMIC: VIEWS ON VACCINATION- AND INFECTION-RELATED RISKS
Authors: Ana Boban, Atanas Banchev, Angelika Bátorová, Melen Brinza, Barbara Faganel Kotnik, Letitia Pintilie-Ancuta, Ester Zapotocka
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: The Liberate Life® project aims to provide support and information to patients with haemophilia (PwH) and limit the impact of haemophilia on their quality of life. The impact of coronavirus disease 2019 (COVID-19) on PwH is poorly understood. Despite vaccination being unanimously recommended, PwH or their caregivers may be vaccine-hesitant. Therefore, gaining a deeper understanding of PwH and their caregivers’ experiences with COVID-19 infection and vaccination offers an opportunity to improve patient-oriented information and education. Aims: To gain insight about the preferences and concerns of PwH and their caregivers regarding COVID-19 infection and vaccination in Central and Eastern Europe. Methods: The Liberate Life survey was sponsored by Swedish Orphan Biovitrum (Bratislava, Slovakia) and administered online using the TypeForm™ platform in Bulgaria, Croatia, the Czech Republic, Hungary, Romania, Slovakia and Slovenia. Data collection was performed using Surveysparrow® from 14 February–01 March 2022. Adults and children with haemophilia A or B of any severity and/or their caregivers were eligible to participate in this survey. The survey results are reported using descriptive statistics. Results: Survey respondents (N=274) were either PwH (n=170) or their caregivers (n=104). The majority of respondents did not have a polymerase chain reaction-confirmed COVID-19 infection (57%), and only one respondent was hospitalised because of COVID-19 (<1%). PwH were mostly vaccinated against COVID-19 (80%). Compared with PwH respondents, almost twice as many caregiver respondents had concerns about COVID-19 vaccination (35% versus 19%, respectively). Blood clots (46%) and bleeding risk (32%) were identified as the most common concerns about vaccination. Summary/Conclusion: Most PwH are vaccinated against COVID-19, and concerns around vaccination are notable for caregivers of PwH as well as PwH. This may represent an opportunity for further education. Keywords: Hemophilia A, COVID-19, Hemophilia B, Vaccination
P1643: FIBRIN CLOT PROPERTIES IDENTIFY PATIENTS THAT BENEFIT FROM CATHETER-DIRECTED THROMBOLYSIS: A POST HOC ANALYSIS OF THE CAVA TRIAL
Authors: Aaron F.J. Iding, Alkarithi Ghadir, Hugo Ten Cate, Robert A.S. Ariëns, Arina J. Ten Cate-Hoek
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Catheter-directed thrombolysis (CDT) to improve patency after deep vein thrombosis (DVT) has not conclusively been shown to prevent the post-thrombotic syndrome in randomized-controlled trials. However, additional CDT might benefit selected patients that are unlikely to attain patency with standard treatment. Aims: We assessed whether fibrin clot properties are associated with long-term patency in patients with iliofemoral DVT. Methods: Patients included in the CAVA trial had blood samples taken at inclusion and at 12 months. Properties of fibrin clot formation and lysis in plasma were determined using turbidity assays, permeation, and confocal microscopy. Patency was defined as >90% iliofemoral vein compressibility on ultrasound assessment at 12 months. The medical ethics committee approved this study, and all patients gave written informed consent. Results: Of 152 patients, 67 remained after excluding patients without blood samples (n=65), without ultrasound assessment (n=8) or with unmeasurable samples at inclusion (n=12), likely due to low-molecular-weight heparin treatment. Patients’ clinical characteristics did not differ between treatment groups. Patency was attained in 50.0% (14/28) of patients with CDT and 25.6% (10/39) of those with standard treatment (p=0.040). In patients on standard treatment not reaching patency, clot properties at inclusion showed shorter lag time, higher maximal clotting rate and higher maximal turbidity, while clot properties were not associated with patency in patients with CDT. No differences were observed at 12 months. Maximal turbidity most accurately predicted patency (Figure 1). In patients with high maximal turbidity, none attainted patency with standard treatment while 44.4% achieved patency with CDT (p=0.012). In contrast, patency did not differ between treatment groups in patients with low maximal turbidity. Summary/Conclusion: Fibrin clot properties, especially maximal turbidity, could identify patients unlikely to attain patency with standard treatment. This predictor might be used to select patients that would benefit from CDT in a point-of-care setting.Keywords: Venous thrombosis, Deep venous thrombosis, Post-thrombotic syndrome, Venous thromboembolism
PB2623: AVATROMBOPAG FOR THE TREATMENT OF CHILDREN WITH PERSISTENT AND CHRONIC IMMUNE THROMBOCYTOPENIA
Authors: Qi An, Lu Liu, Dandan Wang
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: The treatment of persistent and chronic immune thrombocytopenia (ITP) in children is still confusing. Avatrombopag is an orally administered second generation thrombopoietin receptor agonist (TPO-RA). Aims: The aim of the study is to evaluate the efficacy and safety of avatrombopag for children with persistent and chronic immune thrombocytopenia. Methods: we retrospectively analyzed the effect of avatrombopag in children with persistent and chronic ITP. Twenty children with persistent and chronic ITP and a platelet count <30×10^9/L from Xuzhou Children’s Hospital were enrolled in the study from April 2022 to January 2023. The clinical date and the rate of platelet response (platelet count ≥50×10^9/L) was evaluated. The dose of avatrombopag was oral administration once a day with meals started from 20mg/day for ≥6 years of age, 10mg/day for＜6 years of age for 30 to 90 days. Results: Among 20 cases, 8 were males and 12 females, the age of starting avatrombopag was 7.3 (2.1~13.4) years with a mean ITP duration of 21.3 (3~72) months. Before administion of avatrombopag, baseline platelet count was 18.9±10.6×10^9/L. At day 8, platelet count was increased significantly to179.4±156.1×10^9/L. (P<0.01). At day 15, platelet counts was 179.4±156.1×10^9/L (P<0.01).At day 90, platelet counts was 158.3±74.8×10^9/L (P<0.01).At day 8、15、30、60、90, a platelet response (≥50×10^9/L) was 78%（14/18）、83%(15/18)、88%(14/16)、100%(15/15) and 93%(14/15) respectively. Avatrombopag was generally well tolerated, 1 case of headache, 2 cases of epistaxis and petechiae. Summary/Conclusion: In the treatment of persistent and chronic ITP in children, avatrombopag can rapidly and effectively improve the platelet count of children with high platelet response rate, good tolerance, and good safety. Keywords: Immune thrombocytopenia (ITP)
PB2701: SAFETY OF 30 MINUTES INFUSION OF RITUXIMAB BIOSIMILAR. A COHORT STUDY.
Authors: Laida Cuevas Palomares, Ernesto Pérez, Ariane Unamunzaga Cilaurren, Xabier Gutierrez Lopez De Ocariz, Buenaventura Buendia Ureña, Carmen Molinillo Fernández, Begoña Benito Ibarrondo, Ana Cordero Osua, Beatriz Benitez Delgado, Miguel Andrés Moralejo, Juan García Albás, Jose Guinea de Castro
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Rituximab (anti-CD20 Ab) is the cornerstone of the treatment of non-Hodgkin B lymphomas. Infusion-related reactions (IRR) are the most common adverse effects. To reduce them, intravenous premedication with antihistamine and acetaminophen is administered prior to rituximab. If no IRR after first infusion, subsequent infusions time takes 3-6 hours. Many centers use the rapid 90-minute infusion (off-label). Since 2017 subcutaneous rituximab formulation is available, that takes 5 minutes of administration. Nevertheless, in order to reduce cost, due to approval of biosimilars, some health providers continue using intravenous rituximab. On the other hand, with COVID pandemic, an effort to reduce visits and day-care hospitals stays has been made. In the current situation, it would be convenient to reduce day-care stay and the nursing care burden. Aims: To evaluate the safety of an ultrarapid infusion of biosimilar rituximab in a total time of 30 minutes by analyzing IRR and adverse events (AE). Methods: Since November 2021, 3 cohorts of ultrafast infusion have been studied as follows: One cohort (Cohort 1) with intravenous premedication with dexchlorpheniramine and acetaminophen, followed by rituximab infusion over 1 hour, and 2 cohorts with rituximab infusion over 30 minutes: Cohort 2: with intravenous premedication, and cohort 3 with oral premedication. IRR and adverse events have been independently reviewed and graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (November 27, 2017). Results: 48 infusions of rituximab have been administered to 35 patients diagnosed with CD20+ lymphoproliferative syndrome. 22 were administered as monotherapy and 27 were administered in combination with chemotherapy. 1 patient received 4 infusions in different cohorts, 1 patient received 3 infusions, and 6 patients received 2 infusions. In terms of safety, there were 5 grade I-II reactions (10.4%) determined by independent observer and 2 (4.1%) by the principal investigator. No grade III-IV infusion reactions occurred. Summary/Conclusion: Our study demonstrates that rituximab infusion in 30 minutes is feasible and safe for patients. The infusion time reduces the workload in day hospital units by reducing the occupation of treatment spots. Regarding the use of subcutaneous rituximab, the administration of rituximab in 30 minutes improves treatment efficiency. Keywords: Lymphoproliferative disorder, Rituximab, Clinical trial
PB2688: OPIOID USE REDUCTION BY OXYCODONE MORPHINE FORMULARY SWITCH
Authors: Carin Hazenberg, Thijs Oude Munnink
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Oxycodone is a likable opioid with high risk for addiction and misuse, and its use has led to a worldwide opioid epidemic. In the Netherlands, the number of oxycodone users in 2021 was 418.120, which was 7% more than in 2020. Furthermore, oxycodone has many drug-drug interactions in clinical practice where morphine often is a better alternative. To reduce the risk of opioid overuse and to avoid drug-drug interactions, the hemato-oncology ward in the UMCG has switched from oxycodone to morphine as the preferred oral opioid for hemato-oncology patients with pain. Aims: We sought to change standard opioid regimen, from prescribing oxycontin/oxycodone to generic morphine, to patients admitted to the hemato-oncology ward. Methods: On November 1st 2021, the oxycodone morphine switch was communicated to all hemato-oncology physicians and nurses by a motivational letter from a hematologist and hemato-oncology pharmacist. The hemato-oncology ward opioid floor stock was adjusted accordingly to facilitate the oxycodone morphine switch. The effect of the oxycodone morphine switch was retrospectively analyzed by measuring oral opioid clinical orders, the average administered morphine equivalent per admitted patient, the percentage of patients with oral opioid discharge prescriptions, and pain measurements using the Numeric Rating Scale (NRS) at rest and during exercise. 2022-Q2 (with 136 admitted patients) was used as post-intervention period and 2021-Q2 (with 160 admitted patients) was used as reference period. Results were corrected for the number of admitted and discharged patients. Results: The oxycodone morphine switch reduced the average administered morphine equivalent per admitted patient by 35% (150 mg/patient in 2021-Q2 and 95 mg/patient in 2022-Q2). The percentage of patients with an oral opioid discharge prescription was reduced by 41% (27% in 2021-Q2 and 16% in 2022-Q2). Percentage of patients with NRS ≥4 (unacceptable pain) in rest was 34% in 2021-Q2 and 31% in 2022-Q2. Percentage of patients with NRS ≥4 during exercise was 35% in 2021-Q2 and 33% in 2022-Q2. Summary/Conclusion: Switching from oxycodone to morphine as the preferred oral opioid for hemato-oncology patients with pain reduces both the oral opioid use during admission and the number of patients with an oral opioid prescription at discharge. Since the reduction in opioid use resulted in no differences in overall pain control, the oxycodone morphine switch warrants further implementation.Figure 1: number of clinical prescriptions for opioids at the hematology ward Keywords: Drug interaction, Side effects, Quality of life
PB1729: RETROSPECTIVE STUDY OF MAINTENANCE THERAPY WITH CHIDAMIDE AFTER TRANSPLANTATION FOR PATIENTS WITH HIGH RISK T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA
Authors: Xueying Wang, Yan Deng, Lilan Zhang, Guangcui He, Sihan Lai, Shan Zhang, Ying He, Ying Han, Yi Su, Hai Yi
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a highly aggressive type of hematological cancer with poor prognosis. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is currently one of the most effective treatment strategies, however, post-transplantation relapse is still the most important factor influencing prognosis. Here we explore the effect of Chidamide, a novel antineoplastic drug, in maintenance therapy after Allo-HSCT in T-ALL/LBL. Aims: To investigate the efficacy and safety of Chidamide in maintenance therapy after Allo-HSCT for patients with T-ALL/LBL. Methods: The clinical data of six patients with high-risk T-ALL/LBL who received allo-HSCT and post-transplant maintenance therapy with Chidamide from November 2019 to February 2023 was collected. The efficacy and safety were retrospectively analyzed. The minimal residual disease (MRD), acute and chronic graft versus host disease (GVHD), progression-free survival (PFS) rate, overall survival (OS) rate and side effect of Chidamide were analyzed. Results: All of the six patients achieved complete remission and MRD negativity within 30 days after transplantation, including 1 case who previously have central nervous system leukemia (CNSL). 2/6 patients developed grade I-II acute GVHD, and no grade III-IV acute GVHD or any grade chronic GVHD was observed. The median follow-up period was 21 (12-37) months, 2/6 patients relapsed in 5 and 6 months after transplantation respectively. They obtained salvage therapy and still alive with sustain remission. The median survival time was 21 (12-37) months, the 1-year OS rate was 100%, and the 1-year PFS rate was 66.7%. The main adverse effects of Chidamide after transplantation were hematologic adverse effects, mainly manifested as thrombocytopenia (grade 2-3), neutropenia (grade 1-4) and anemia (grade 3), which were improved by extending the interval of Chidamide. One patient developed fatigue (grade 1), 2 patients developed nausea and vomiting (grade 1), 2 patients developed abnormal liver function (grade 2). The symptoms were easily relieved by symptomatic treatment. Summary/Conclusion: This study demonstrates that maintenance therapy with Chidamide after transplantation is safe and effective for high-risk T-ALL/LBL patients and need further investigation. Keywords: T cell lymphoma, Allogeneic hematopoietic stem cell transplant, HDAC inhibitor, T cell acute lymphoblastic leukemia
PB2664: GENES POLYMORPHISM OF FOLATE PATHWAY ENZYMES IN WOMEN WITH RECURRENT PREGNANCY LOSS
Authors: Anastasia Zagarskikh
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Currently, there is no unified understanding of the causes of reproductive disorders. Among their diversity, hyperhomocysteinemia is noted, which is considered as a biomarker of prothrombotic conditions and an unsuccessful pregnancy outcome due to the transformation of the main methyl group of human cell metabolism. Disruption of the functioning of DNA methylation processes in somatic and germ cells leads to the impossibility of conception or loss of pregnancy. Aims: To assess the frequency of genetic polymorphisms in folate cycle metabolic pathway (MTHFR: 677 C>T, MTHFR: 1298 A>C, MTR: 2756 A>G, MTRR: 66 A>G) in women with reproductive failures and without fertility disorders. Methods: Genetic polymorphisms of folate pathway enzymes in 96 women were analyzed, 33 of them - with recurrent pregnancy loss (ICD-10: N96), with 3 or more missed abortions, and 63 - without obstetric complications, with two or more than urgent deliveries (comparison group). Anatomical, gynecological, infectious and endocrine causes of miscarriages are excluded. The study was carried out with reagents and equipment of “DNA Technology”, Russia). Statistical data processing used the χ2 test and relative risk calculation. Results: The distribution of polymorphic genes of the folate cycle is presented in the table. In women with recurrent pregnancy loss, there was a high detectability of genotypes with the C allele of the MTHFR:1298 A>C gene (63.6% and 38.7%; χ2=5.4; RR=1.6) and a decrease in the frequency of occurrence of wild-type homozygotes of the same gene (36.4% and 61.3%; χ2=5.4; RR=0.6) to the comparison group. In accordance with the value of the relative risk (RR), the probability of recurrent pregnancy loss in woman with the C allele of the MTHFR:1298 A>C gene was 1.6 times higher than in those without this polymorphism. Tabl. Frequency of occurrence of folate cycle genotypes (%) in women - Polymorphism Genotypes Women with recurrent pregnancy loss (n=33) Comparison group (n=63) MTHFR: 677 C>T С/Т 30,3 46,0 С/С+T/Т 69,7 54,0 MTHFR: 1298 A>C A/A 36,4* 61,3 А/С+С/С 63,6* 38,7 MTR: 2756 A>G A/A 66,7 67,7 A/G+G/G 33,3 32,3 MTRR: 66 A>G A/A 18,2 8,1 A/G+G/G 81,8 91,9 Note: * p<0.05, statistically significant differences between groups Summary/Conclusion: The predisposition of women to recurrent pregnancy loss was established depending on the presence of the allele C of the MTHFR: 1298 A>C gene with a significantly high probability of this complication of pregnancy. Keywords: Methylene tetrahydrofolate reductase, Pregnancy, Gene polymorphism
The exercise IL-6 enigma in cancer
Authors: Samuel T. Orange, Jack Leslie, Mark Ross, Derek A. Mann, Henning Wackerhage
Journal: Trends in Endocrinology and Metabolism (2023)

Interleukin (IL)-6 elicits both anticancer and procancer effects depending on the context, which we have termed the 'exercise IL-6 enigma'. IL-6 is released from skeletal muscles during exercise to regulate short-term energy availability. Exercise-induced IL-6 provokes biological effects that may protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilising immune cells, and reducing DNA damage in early malignant cells. By contrast, IL-6 continuously produced by leukocytes in inflammatory sites drives tumorigenesis by promoting chronic inflammation and activating tumour-promoting signalling pathways. How can a molecule have such opposing effects on cancer? Here, we review the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and define the factors that underpin the exercise IL-6 enigma.
Equity, diversity, and inclusion at the Global Alliance for Genomics and Health
Authors: Neerjah Skantharajah, Shakuntala Baichoo, Tiffany F. Boughtwood, Esmeralda Casas-Silva, Subhashini Chandrasekharan, Sanjay M. Dave, Khalid A. Fakhro, Aida B. Falcon de Vargas, Sylvia S. Gayle, Vivek K. Gupta, Rachele Hendricks-Sturrup, Ashley E. Hobb, Stephanie Li, Bastien Llamas, Catalina Lopez-Correa, Mavis Machirori, Jorge Melendez-Zajgla, Mareike A. Millner, Angela J.H. Page, Laura D. Paglione, Maili C. Raven-Adams, Lindsay Smith, Ericka M. Thomas, Judit Kumuthini, Manuel Corpas
Journal: Cell Genomics (2023)

A lack of diversity in genomics for health continues to hinder equitable leadership and access to precision medicine approaches for underrepresented populations. To avoid perpetuating biases within the genomics workforce and genomic data collection practices, equity, diversity, and inclusion (EDI) must be addressed. This paper documents the journey taken by the Global Alliance for Genomics and Health (a genomics-based standard-setting and policy-framing organization) to create a more equitable, diverse, and inclusive environment for its standards and members. Initial steps include the creation of two groups: the Equity, Diversity, and Inclusion Advisory Group and the Regulatory and Ethics Diversity Group. Following a framework that we call "Reflected in our Teams, Reflected in our Standards," both groups address EDI at different stages in their policy development process.
Expanding the genetic landscape of obesity
Authors: Jian Yang
Journal: Cell Genomics (2023)

In a recent Cell Genomics article, Kaisinger, Kentistou, Stankovic, et al.1 use a large-scale exome sequencing study in the UK Biobank to identify rare gene variants associated with sex-specific and life-course effects on obesity. Jian Yang discusses the authors' findings and wider context in obesity research in this preview.